ChemInform Abstract: 6,9‐Bis((aminoalkyl)amino)benzo(g)isoquinoline‐5,10‐diones. A Novel Class of Chromophore‐Modified Antitumor Anthracene‐9,10‐diones: Synthesis and Antitumor Evaluations.

Abstract

6,9-Bis((aminoalkyl)amino)benzo(g)isoquinoline-5,10-diones.A Novel Class of Chromophore-Modified Antitumor Anthracene-9,10diones: Synthesis and Antitumor Evaluations.-In a search for analogues with optimal therapeutic efficacy, a series of aza analogues of (I) is prepared by reaction of (V) with the appropriate amines in a similar manner as described for (IIa) (isolated as hydrochloride). Mitoxantrone (I) is a known antitumor agent, accompanied by toxic side effects. Compounds (IIb) and (IIc) show in vitro activities against L1210 murine leukemia similar to (I), but all aza analogues have decreased cytotoxic potency in both the sensitive and the doxorubicin-resistant LoVo human colon adenocarcinoma cell line compared with (I). In vivo antitumor activity against P388 murine leukemia of (IIb) and (IId) is comparable and of (IIa) superior to that of (I). Therefore (IIa), which is not cardiotoxic and less leukopenic than (I), appears to be the most promising aza analogue for further clinical evaluation. -(KRAPCHO, A. P.; PETRY, M. E.; GETAHUN, Z.; LANDI, J. J. JUN.; STALLMAN, J.; POLSENBERG, J. F.; GALLAGHER, C. E.; MARESCH, M. J.; HACKER, M. P.; GIULIANI, F. C.; BEGGIOLIN, G.; PEZZONI, G.; MENTA, E.; MANZOTTI, C.; OLIVA, A.; SPINELLI, S.; TOGNELLA, S.; J. Med. Chem. 37 (1994) 6, 828-837; Dep.

Anthraquinone derivative O,O′-bis-(3′-iodopropyl)-1,4-dihidroxyanthraquinone modulates immune response and improves experimental autoimmune encephalomyelitis

“…Different studies related the presence of these groups to cytotoxicity and notably the cardiotoxicity of mitoxantrone [16][17][18][19]. The concentration of 25μg/ml in the in vitro tests was used to determine a parameter between MIT and DIPDHAQ in higher doses.…”

Synthesis and biological evaluation of new naphthoquinone‐containing pyrrolo‐thiazoles as anticancer agents

“…However, in the case of quinones others suggest that planarity is an important factor to achieve biological activity because DNA intercalation is another possible mechanism of action [6]. For anthracene‐9,10‐diones which interfere with topoisomerase II, the derivatives need to be planar and also need another structural feature, like alkyl amino side chains, to interact with protein as observed for mixoxantrone [32]. In our case, the very planar structure of the benzo[ f ]thiazolo[4,3‐ a ]isoindole‐6,11(1 H ,3 H )‐diones caused by the extended conjugation is not sufficient to allow a high anticancer activity possible because of the lack of this type of side chains.…”

Anthraquinones as Artificial DNA Building Blocks

“…[30,31] They are a frequently found motif in DNA targeting drugs. [30,[32][33][34][35][36] Not surprisingly, conjugation of anthraquinone to oligonucleotides has served as a common strategy for the development of high affinity oligonucleotides. [37][38][39][40][41][42][43][44][45] Furthermore, the low reduction potential of anthraquinone derivatives opens possibilities for charge transport through DNA [46][47][48][49][50] and electrochemical DNA sensing.…”